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| United States Patent |
5,650,157
|
|
Bockow
|
July 22, 1997
|
Pharmaceutical compositions and methods
Abstract
Some otherwise desirable oil compositions derived from natural sources are
characterized by an unpleasant odor. Fractions or combinations of such
oils may also be so characterized. Stable, deodorized oils may be prepared
by adding an amount of a deodorizing agent effective to substantially
reduce the odor of the derived oil composition, fraction or combination
thereof to that oil composition, fraction or combination. The
pharmaceutical topical compositions of the present invention contain these
stable, deodorized oil compositions and exhibit enhanced penetration
properties and achieve enhanced patient response. The improved
pharmaceutical compositions of the present invention may be used to manage
pain and/or to treat the underlying ailments. Methods of making such
topical pharmaceutical compositions are also discussed.
| Inventors:
|
Bockow; Barry I. (16122 8th Ave. SW., Seattle, WA 98166)
|
| Appl. No.:
|
247682 |
| Filed:
|
March 22, 1994 |
| Current U.S. Class: |
424/401; 424/523; 424/769 |
| Intern'l Class: |
A61K 006/00 |
| Field of Search: |
424/401,523,195.1
|
References Cited
U.S. Patent Documents
| 4505902 | Mar., 1985 | Millard | 424/195.
|
| 4710383 | Dec., 1987 | Dick | 424/449.
|
| 4816271 | Mar., 1989 | Scaffidi | 424/60.
|
| 4847071 | Jul., 1989 | Bissett | 424/59.
|
| 4954332 | Sep., 1990 | Bissett | 424/59.
|
Primary Examiner: Phelan; D. Gabrielle
Attorney, Agent or Firm: Seed and Berry LLP
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. Ser. No. 08/053,508, filed Apr.
26, 1993, now abandoned, which is a continuation of U.S. Ser. No.
08/816,833, filed Dec. 30, 1991, abandoned, which is a continuation of
U.S. Ser. No. 07/545,414, filed Jun. 27, 1990, abandoned, which is a
continuation in part of U.S. Ser. No. 07/520,026, filed May 7, 1990, now
abandoned.
Claims
What is claimed is:
1. A topical pharmaceutical preparation comprising a marine oil rich in
omega-3 fatty acid, a deodorizing agent, and an effective amount of a
pharmaceutically active ingredient, wherein the omega-3 fatty acid is at
least 2% by weight of the preparation, and wherein the pharmaceutically
active ingredient is selected from anti-inflammatory agents, analgesics,
vasodilatory agents, anti-pruritic agents, anesthetics, counterirritants,
astringents, antiseptics, keratolytic agents, anticholinergic agents,
antihistamines, wound healing agents, and combinations thereof.
2. The topical pharmaceutical preparation of claim 1 wherein the omega-3
fatty acid is at least 3% by weight of the preparation.
3. The topical pharmaceutical preparation of claim 1 wherein the omega-3
fatty acid is at least 10% by weight of the preparation.
4. The topical pharmaceutical preparation of claim 1 wherein the omega-3
fatty acid is present in mono-, di- or tri-glyceride form.
5. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is selected from an anti-inflammatory
agent, an analgesic, and a combination thereof.
6. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is salicylic acid.
7. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is methyl salicylate.
8. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is benzocaine.
9. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an anti-inflammatory agent.
10. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an analgesic.
11. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is a vasodilatory agent.
12. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an anti-pruritic agent.
13. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an anesthetic.
14. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is a counterirritant.
15. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an astringent.
16. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an antiseptic.
17. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is a keratolytic agent.
18. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an anticholinergic agent.
19. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is an antihistamine.
20. The topical pharmaceutical preparation of claim 1 wherein the
pharmaceutically active ingredient is a wound healing agent.
Description
FIELD OF THE INVENTION
The present invention involves stable, deodorized oils and compositions
containing such oils, wherein the oil component of the deodorized oil or
the composition containing same has an unpleasant odor when standing alone
without the benefit of conventional chemical processing for deodorization.
The stable, deodorized oils of the present invention are prepared without
conventional deodorization processing that adversely impacts oil stability
and changes the chemical composition of the oil. More specifically, the
present invention involves pharmaceutical compositions containing an
active medicament and a stable, deodorized oil.
BACKGROUND OF THE INVENTION
Oils have many advantageous properties. Many cosmetic compositions contain
fats and oils or materials derived from such fats and oils that serve as
emollients and/or lubricants therein. Exemplary of such materials are
triglyceride esters, fatty acids, fatty alcohols, soaps, detergents,
cationic antiseptic and softener rinses, alkyl fatty acid esters,
polyhydric alcohol esters, ethoxylated fatty alcohols, ethoxylated fatty
ethers, ethoxylated sorbitan esters, branched-chain high-molecular weight
alkyl esters, lanolin-derived fatty acids and fatty alcohols, other
lanolin derivatives, and the like. In the pharmaceutical field, oils and
fats are also used as emollients and/or lubricants in topical
compositions, castor oil is useful as a cathartic, while chaulmoogra oil
is used to treat Hansen's disease. Also, corn, sesame and cottonseed oils,
for example, are employed as carriers for fat-soluble substances.
Marine animal oil compositions, in particular, have been suggested for a
variety of uses as dietary supplements. For example, marine oil
compositions are alleged to decrease cholesterol and triglycerides levels
in humans, decrease prostaglandin synthesis, inhibit platelet aggregation
and the like. Moreover, food processing concepts are being investigated to
increase dietary intake of marine oils. Some proposals include
incorporating fish oils into a wide variety of products, such as pastes
and spreads, butter analogs and margarines, salad dressings, dairy foods,
oils and oil blends, sausage, and smoked and spiced foods. Marine oil
compositions or derivatives there of have also been used in both cosmetic
and therapeutic topical formulations. For example, shark liver oil has
been determined to be useful for the temporary protection of minor cuts,
scrapes, burns and sunburn, and for the prevention and temporary
protection of chafed, chapped or windburned skin and lips.
A non-fatty acid/ester component of marine oil compositions, often
isolated, hydrogenated and included in topical compositions, is squalene,
an unsaturated hydrocarbon C.sub.30 H.sub.50. Squalene is also a component
of adult human skin surface lipids. Squalene, itself, is not typically
used in topical compositions due to its susceptibility to oxidation,
resulting in formation of undesirable oxidation products. Primarily for
this reason, squalene (hydrogenated squalene, also found in high
concentrations in human skin surface lipids and obtained through chemical
processing of squalene) is the hydrocarbon most often included in topical
compositions.
While oral dosage forms containing oils, such as fish oils, have been
developed and marketed as dietary supplements, the usefulness of topical
preparations containing these oils has been limited by the unpleasant odor
associated with such oils. When a composition is applied topically, any
odor associated therewith becomes associated with the skin to which it is
applied. As a result, consumer acceptability of topical compositions is
highly influenced by the aroma thereof. Consequently, topical compositions
having a malodorous oil component would not enjoy success in the
marketplace.
The "off" or "rancid" odor associated with oils is produced, in part, by
oxidation of polyunsaturated fatty acids contained therein. Since highly
unsaturated fatty acids occur in greater proportion in marine animal oils
than in common land animal and vegetable fats and oils, rancidity is a
greater problem when using marine animal oils. Oxidation of
polyunsaturated fatty acids leads to the formation of hydroperoxides. The
decomposition products of these hydroperoxides, such as aldehydes
resulting from oxidation of marine animal oils, exhibit the unpleasant
odors characteristic of rancid oils. Certain decomposition intermediates
have also been suggested to contribute to the unpleasant odor of some
oxidized oils.
The "inherent" or "bland" odor of oils does not appear to arise from
volatile components of oil compositions, which could be easily removed
therefrom. Instead, these odors appear to be characteristic of the fatty
acids or long-chain hydrocarbons associated therewith in natural oil
compositions. In fish oils, for example, the "fishy" odor is postulated to
be the result of interaction during oxidation between nitrogenous moieties
and unsaturated glycerides present in the oil composition. Another theory
regarding the source of the odor is that the unsaponifiable fraction
(i.e., 5 hydrocarbon, sterol, methyl sterol, long-chain alcohol,
triterpene alcohol, pigment, trace materials and the like) of the oil
composition is the component with which the "fishy" odor is associated. In
any event, this odor is not permanently removable even by drastic steam
deodorization procedures (i.e., prolonged vacuum treatment at elevated
temperatures, such as from about 230.degree. to 260.degree. C.). The odor
returns upon exposure of the "deodorized" oil to oxygen.
Since marine oils are capable of imparting advantageous properties to
topical compositions, efforts have been made to overcome the aroma
problem. These efforts were complicated by the fact that many processes
alter the composition of fats and fatty acids. Exemplary processing
techniques are refining, high temperature clay bleaching, high
temperature-high pressure fat splitting, distillation of fatty acids,
molecular distillation of monoglycerides, transesterification reactions
and partial hydrogenation. Alterations arising from processing include
cis-trans isomerization, conjugation of polyunsaturates, polymerization,
dehydration and the like.
Two strategies have emerged for using malodorous oils in topical
compositions. In the first, only amounts of oil small enough not to
adversely impact the odor of the complete topical composition were used.
This strategy is not effective when higher concentrations of oil are
required or desireable to impart advantageous properties to topical
compositions.
Alternatively, to increase the percentage of oil which may be used within
commercially acceptable topical compositions, chemical deodorization was
explored. Barlow S. M. and Stansby M. E., eds., "Nutritional Evaluation of
Long-Chain Fatty Acids in Fish Oil", page 20 Academic Press, London, 1982
describe a deodorization process featuring steam distillation conducted
under a vacuum. The primary operating unit is a steel shell having trays
disposed therein, maintained at from 2 to 5 mm Hg absolute pressure. The
oil composition is heated to a process temperature of about 220.degree. to
250.degree. C. by steam, and volatiles, which adversely impact oxidative
stability, are removed from the unit. Typical refining processes are also
discussed in "Nutritional Evaluation of Long-Chain Fatty Acids in Fish
Oil" at pages 13-20. Such refining processes include crude oil storage (to
remove oil insolubles), degumming, neutralization, water washing, drying,
bleaching, filtration, deodorization, polishing and the like.
Problems arose during the deodorization and refining processes, however, in
that the processing steps changed the chemical composition of the oil
itself (i.e., the composition being deodorized that resulted from minimal
refining of the oil). For example, natural antioxidants, such as the
various tocopherols which constitute vitamin E, were often either removed
from the oil composition, broken down or chemically altered to such an
extent that those antioxidants were functionally destroyed or impaired
during deodorization or other oil processing. See, for example, Bailey's
Industrial Oil and Fat Products, Volume 1, Fourth Ed., page 75, Daniel
Swern, ed., John Wiley & Sons, New York, 1979. Caustic and steam oil
refining processes remove at least a portion of tocopherol compounds from
oil compositions. Carbon treatment of oil compositions also results in
antioxidant removal. It has been determined that even small amounts of
antioxidant may be sufficient to cause an increase in both resistance to
oxidation and amount of oxidation required to produce rancidity. Primarily
for this reason, natural fats containing antioxidants are much more
resistant to oxidation than their pure triglyceride counterparts.
Since unsaturated fat and fatty acid components of an oil composition, such
as triglycerides, diglycerides, alkoxydiglycerides (i.e., glycerol
ethers), monoglycerides, omega-3 fatty acids, omega-9 fatty acids and the
like, are susceptible to oxidation when exposed to air, the absence of
these natural antioxidants from the oil composition leads to a decrease in
the stability thereof. Bailey's Industrial Oil and Fat Products defines
stability "as the resistance to autoxidation under prescribed conditions
of aging . . . measured in units of time required for the product to (a)
acquire a state of oxidation which can be correlated with organoleptic
detection of rancid odor and flavor, or (b) to reach the end of the
induction period if oxygen absorption measurement or peroxide analysis is
used." The induction period is the time frame in which antioxidants
effectively protect against oxidation. Once rapid oxidation sets in,
antioxidants have little or no ability to curtail the reaction.
Consequently, the presence of antioxidants in a composition constitutes a
preventive measure rather than a corrective one.
Decomposition via oxidation can also cause a decrease in the percentage of
unsaponifiable matter contained in an oil composition through oxidative
degradation of hydrocarbons. Saponification is the reaction of a fatty
acid, for example, with a base to produce a salt. Hydrocarbons, for
example, cannot undergo such a reaction and are, thus, unsaponifiable.
Exemplary unsaponifiable hydrocarbons found in oil compositions are
squalene, gaducene, pristane, zamene, citorhenene and the like. The
hydrocarbon squalene exhibits antioxidant activity under certain
circumstances. Squalene also enhances percutaneous absorption of vitamin A
and serves as a protective agent for human sebum. Other exemplary
unsaponifiable components of fish oil are sterol, methyl sterol,
long-chain alcohol, triterpene alcohol, pigment, trace materials, and the
like.
Topical compositions are typically stored for some time prior to
application thereof, and often are left standing open by users between
such applications. Thus, stability of each component within a topical
composition is considered in assessing the usefulness of the topical
composition as a whole. A decrease in the stability of any component
decreases the utility of the topical composition in which the component is
dispersed. Moreover, antioxidants are not compound-specific protectants.
That is, tocopherols dispersed in a topical composition would protect
fatty acids, hydrocarbons and any other oxidation-susceptible component of
that topical composition from oxidation. Thus, chemical deodorization of
the oil composition can create stability problems for the topical product
containing the oil composition by functionally impairing or destroying
natural antioxidants.
Other, non-fatty acid components of an oil composition, such as vitamins,
pro-vitamins (i.e., precursors of vitamins which are converted to vitamins
in vivo), neovitamtns (i.e., isomeric forms of vitamins that function as
vitamins in vivo), sterols, phosphatides, hydrocarbons and the like, may
also be removed, functionally destroyed or functionally impaired during
the deodorization or other oil processing. Alkali refining, for example,
may significantly reduce the vitamin A content of oils, and carbon
treatment of the oil composition may render the vitamin A component
unstable. Hydrogenation processing may saturate vitamin A and decrease the
biological activity thereof, unless precautions to preserve vitamin A
activity are taken. Also, high temperature treatments, such as steam
deodorization, decompose vitamin A provitamins.
These additional oil composition components, if intact, may also contribute
other desirable properties to the topical composition as a whole. For
example, vitamins, such as vitamin D and vitamin A, often significant
components of oil compositions, serve certain biological functions.
Vitamin E exhibits antioxidant properties as well as other vitamin E
activity. Further, interrelation hips between the functions of vitamin A
and vitamin E have been noted and attributed, in part, to the protective
action of vitamin E with respect to vitamin A. Sterols, such as
cholesterol, impart sterol activity in vivo. Phosphatides provide
reinforcement to the action of other antioxidants.
It has now been recognized in the present invention that a substantially
intact oil composition (i.e., a composition in which the components
thereof are maintained in a form substantially equivalent to the natural
form of those components) imparts advantageous properties to the ultimate
topical composition containing the oil composition. The natural form of
each of the components of the oil composition ingredient of the ultimate
topical composition of the present invention is that form in which those
components exist prior to refining. When chemical deodorizing processes
are used, such components are modified and, as a result, chemical
deodorization adversely impacts the ability of the oil component of the
topical composition to impart advantageous properties to the ultimate
topical composition.
Moreover, the natural form of the oil composition components typically
includes one or more specific isomeric forms thereof. Other isomers may be
created through oxidation, hydrogenation, partial hydrogenation, high
temperature treatments and the like. For example, U.S. Pat. No. 4,843,095
indicates that saponification reactions converting triglyceride oil
components to free fatty acids, if conducted under certain conditions,
result in isomerization via cis-trans conversion. That is, the fatty acids
resulting from the reaction do not correspond isometrically to the
original triglyceride starting material. In addition, prior oil containing
compositions were stabilized by hydrogenating the oil. It has now been
discovered that hydrogenated fatty acids exhibit inferior penetration
abilities in comparison with the natural polyunsaturated form of the fatty
acids.
Estimates indicate that more than 35,000,000 U.S. adults and children
suffer from pain. Some of these sufferers exhibit concomitant inflammatory
conditions such as rheumatoid or psortatic arthritis. Other patients,
however, do not fall into the inflammation category, but have a wide
variety of musculoskeletal ailments including myofascial pain syndrome,
tendoniris, bursitis, ligament attachment conditions or soft tissue
complaints. An additional subset of patients exhibit chronic low-back pain
that is not inflammatory but, nevertheless, requires pain management.
Short-lived acute problems, such as tennis elbow, bursiris, and hip
pointers, would also benefit from some form of pain management. Post
trauma pain sufferers who have sustained ligamentous tears, miniscal
tears, contusions, fractures or the like are another important patient
subset. Metabolically-caused pain (i.e., gout, pseudogout, osteoporosis,
primary underlying bone disease such as Paget's disease) requires
management. In addition, treatment of patients with primary or secondary
cancer are problematic for the clinician in view of these patient's pain
management needs.
Almost all of the aforementioned patients suffering pain will be treated by
physicians with nonsteroidal anti-inflammatory drugs, consisting primarily
of chemical variations of ibuprofen. Regardless of the length of the
half-lives of these routinely used drugs, administration thereof can
result in serious undesirable side-effects. Estimates indicate that
approximately 5% of the patients who receive these drugs will develop an
NSAID-induced gastropathy that can lead to peptic ulceration, bleeding,
hemorrhage, and even death. Moreover, patients in this 5% bracket are
asymptomatic, and, as a result their first presentation to a hospital
typically results from a GI hemorrhage. Other problems which may arise
from the administration of anti-inflammatory drugs are compromised renal
function, dermatological or cutaneous reactions, drug-induced hepatitis,
enhanced salt retention, and, in rare cases, potentially fatal bone marrow
depression. Patients with high blood pressure must be monitored carefully
when being treated to manage pain, because the patient's hypertension may
be augmented by the pain medication. Also, pain treatment available to
children are severely limited as a result of the side-effects of these
anti-inflammatory medications.
Given the problems incumbent in this entire class of medication, it is
desirable to provide a therapeutic option allowing effective pain
management with decreased risk of deleterious side-effects. It has been
recognized by the present inventors that topical administration of
anti-inflammatory agents may provide such an alternative. When
administered directly to the afflicted area, high levels of the medicament
may be directly delivered to produce a significant therapeutic response.
Thus, preparations containing oils or fractions or combinations thereof,
which do not exude the unpleasant odor characteristic of such oils or oil
fractions or combinations would be useful. In addition, since it has now
been recognized that topical compositions containing oil compositions,
with the components thereof maintained in their naturally occurring state
stably therein (i.e., exhibiting no substantial chemical breakdown or
alteration of those oil components) offer advantages over topical
compositions containing conventionally processed oil compositions,
maintenance of the components of an oil composition ingredient of a
topical composition in a form substantially the same as its natural form
during and after deodorization is desireable.
SUMMARY OF THE INVENTION
The present invention features pharmaceutical topical compositions
containing a stable, deodorized oil, a fraction, or a combinations thereof
and an active pharmaceutical ingredient. The active pharmaceutical
component of the compositions of the present invention do not
substantially adversely affect the structure and/or function of the oil
component. Additional biologically acceptable adjuvants may be added to
the topical compositions of the present invention. Preferred
pharmaceutical components of the pharmaceutical topical compositions of
the present invention are anti-inflammatory agents, analgesics,
vasodilatory agents, anti-pruritic agents, anesthetics, protectants,
counter irritants, astringents, antiseptics, keratolytic agents,
anticholinergic agents, antihistamines, wound healing agents, and
combinations thereof.
The stable, deodorized oils of the present invention, are capable of being
used in topical compositions at high concentrations without imparting an
unpleasant odor to such compositions. In accordance with the present
invention, a stable, deodorized oil is a composition of matter including
an oil composition characterized by an unpleasant odor or a fraction or
combination of such oils so characterized and an amount of aloe effective
to substantially deodorize the oil or fraction or combination thereof. A
preferred embodiment of the oil useful in pharmaceutical compositions of
the present invention is a stable, deodorized oil containing marine oils
or omega-3 fatty acids. In addition to improved odor characteristics, the
stable, deodorized oil of the present invention also exhibits enhanced
skin-penetrating capability and imparts such enhanced capability to
topical compositions containing the oil.
The pharmaceutical topical compositions of the present invention may be
prepared by a process involving the steps of: admixing the malodorous oil
composition or fraction or combination thereof with aloe; aging the
mixture; and admixing the pharmaceutical ingredient and other adjuvants
and the aged mixture. An alternative process for preparation of
compositions in accordance with the present invention involves the steps
of: admixing the malodorous oil composition or fraction or combination
thereof, aloe, the pharmaceutical component, and other adjuvants; and
aging the mixture.
DESCRIPTION OF PREFERRED EMBODIMENTS
As used in this specification, the term "oil composition" indicates a
composition containing fats and/or fatty acids and other components
derived from a natural oil source. Derivation may constitute minimal
refining of the crude oil alone or include other processing, such as
fractionation or combination of the oil composition. A synthetically
prepared oil composition could be deodorized in accordance with the
present invention, if necessary.
"Stable, deodorized oil composition", as used in this specification, is
indicative of an oil composition in admixture with a deodorizing agent,
such as aloe, capable of deodorizing the oil composition.
The term "topical composition", as used in this specification, indicates a
composition containing a stable, deodorized oil composition in combination
with a single or a plurality of topical adjuvants which do not interfere
with the structure and/or function of the oil component.
An oil that may be stably deodorized in accordance with the present
invention is any oil composition characterized by an unpleasant odor or a
fraction or combination of oil compositions so characterized. In a
preferred embodiment of the present invention, the oil composition is
derived from a marine source. Exemplary sources of marine oils are fish,
fish livers, shellfish, marine mammals and the like. Exemplary fish from
which the preferred oils of the present invention may be derived are
sharks, such as dogfish, bramble, Greenland, rough, saw, angel, bullhead,
carpet, sand, tiger, thresher, basking, mackerel, cat, hound, weasel,
requiem, hammerhead, sleeper and soupfin; cod, such as atlantic and
pacific; herring, such as menhaden and anchovy; mackerel, such as common;
haddock; halibut, such as pacific; perch, such as ocean; mullet, such as
striped; pilchard; salmon, such as king, silver, sockeye, chinook, chum,
coho and pink; sole, such as lemon; trout such as rainbow; tuna, such as
bluefin, skipjack, albacore and yellowfin; whitefish, such as lake;
pollock; ratfish; carp; flounder; hake; rockfish; sardines; whiting;
sablefish; swordfish; and the like. Exemplary fish from which fish liver
oil may be obtained are cod, such as atlantic; haddock; herring, such as
pacific and atlantic; menhaden; pacific rockfish; pacific sablefish;
pacific salmon, such as king, silver, chum, sockeye, pink; shark, such as
dogfish, bramble, Greenland, rough, saw, angel, bullhead, carpet, sand,
tiger, thresher, basking, mackerel, cat, hound, weasel, requiem,
hammerhead, sleeper and soupfin; atlantic swordfish; tuna, such as
albacore; saith; ling; dogfish; porbeagle; and the like. Exemplary
shellfish from which oil compositions may be obtained are krill, clam,
such as littleneck; crab, such as blue; oyster, such as pacific; scallop,
such as sea; shrimp; lobster; and the like. Exemplary marine mammals are
seals, whales and the like.
Marine oil compositions vary quite widely. As a result, the marine oil(s)
used as a starting material in preparation of stable, deodorized oils or
topical compositions of the present invention is selected based upon the
desired characteristics of the resulting oil composition. An oil
composition obtained from piked dogfish, for example, is suitable
ingredient for cosmetic and therapeutic topical agents. Greenland sharks
and ratfish oils, for example, have high glycerol ether content and little
vitamin A, while oil obtained from cod livers contains vitamin D. Salmon
oil exhibits high etcosopentaenoic and docosahexaenoic acid contents. As
compositions of various marine oils are known, a practitioner would be
able to select suitable marine oils to achieve a desired oil composition.
The stable, deodorized oil compositions of the present invention may be
derived from crude marine oils. Crude marine oils are obtained by grinding
marine animal body portions and treating the ground material to remove
marine oils therefrom. The exact content of such crude oils vary in
accordance with a variety of factors. Crude oils may contain insoluble,
colloidal and soluble components. Exemplary insoluble components of crude
oil are moisture, rust, dirt and proteins which are not dispersed within a
colloidal suspension. Exemplary colloidal components are proteins,
phosphatides and carbohydrates. Exemplary soluble components are pigments,
oxidation products, trace metals, phosphatides which are not dispersed in
colloidal suspensions, sulphurous and nitrogenous compounds, free fatty
acids, mono-, di- and tri-glycerides and unsaponifiable matter.
The oil composition to be deodorized may be obtained from marine animals by
minimal refining thereof, such as by steam refining as described in
Fishery Leaflet 233 distributed by the Fish & Wildlife Service of the
united States Department of the Interior. Steam refining involves:
grinding of the fish body or fish body portions, such as the liver;
introduction of live steam into tanks containing the ground fish under
agitated conditions; and oil separation by gravity or, preferably, by
three-phase or sludger centrifuge. Fishery Leaflet 233 and U.S. Pat. No.
1,833,061 describe the acid digestion process for minimally processing
crude oil. Fish body parts are ground and treated with an acid to achieve
a pH of approximately 1.5. Subsequently, a cooking step, typically an
incubation period which may optionally take place in temperatures of up to
approximately 70.degree. C. to speed up the process, is accompanied by
agitation. Such subsequent cooking and agitation are employed to enhance
oil separation and/or reinforce the action of other separating substances.
Minimal refining using the acid digestion method is augmented by the
enzymatic action of natural enzymes contained in proteinaceous portions of
marine animals. These natural enzymes promote hydrolysis of marine protein
to facilitate the separation of marine oils therefrom.
A suitable method of minimal processing of marine animal product to obtain
a marine animal oil to be deodorized in accordance with the present
invention is as follows: obtain fresh raw marine animal product having an
oil content of at least about 20%, although a marine animal product of
lower oil content may also be processed in this manner; grind the raw
product; add water, preferably warm water at approximately 25.degree. C.
to increase the activity of the enzymes, in a ratio of from about 1:1 to
about 3:1 water to waste by weight; mix the water and ground marine animal
product until the mixture is uniform; adjust the pH of the mixture (i.e.,
add an acid, such as phosphoric acid or the like thereto) to between about
2.0 and 3.5, with about 2.8 being especially preferred to avoid
decomposition (high pH) and sterilization (low pH) of the slurry; mix
gently to avoid emulsion formation; let mixture stand at room temperature
for approximately 24 hours to allow the oil to separate; repeat the
previous two steps two or three times; draw off oil that has risen to the
top of the mixing vessel; remove any particles suspended in the oil by the
use of gravity filtration and fine or ultra fine filter paper or by
centrifuge; heat oil to approximately 75.degree. C. to enhance the
stability of the oil and permit the oil to cool gradually.
Oil compositions useful within the present invention may be further
processed by fractionation, for example, to obtain oil fractions useful in
the present invention. Exemplary fractions are glycerol ether, vitamin A,
neovitamin A, omega-3 fatty acid, omega-9 fatty acid, hydrocarbon, restim,
and the like. The glycerol ether fraction of an oil composition preferably
contains glycerol ethers of omega-3 fatty acids. Fractionation can be
accomplished via known techniques, such as that described by Malins in
"Fatty Acids and Glycerol Ethers in Alkoxydiglycerides of Dogfish Liver
Oil", reprinted from Chemistry and Industry, 1960, pp. 1359-1360.
Combinations of oil compositions or fractions thereof are also contemplated
by the present invention. Exemplary of such combinations are pink salmon
and piked dogfish, which yields an oil combination of higher stability
than pink salmon alone; and greenland shark and ratfish, yielding an oil
combination having high glycerol ether and low vitamin A contents. Such
combinations may be obtained via known techniques, such as simple mixing.
The preferred oil compositions of the present invention are rich in omega-3
fatty acids. Omega-3 fatty acids are long-chain, polyunsaturated fatty
acids. Exemplary omega-3 fatty acids useful in the present invention are
eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid and
linolenic acids of the omega-3 series and the like.
Oil compositions of the present invention may also contain vitamins, such
as vitamins A, E, D and the like; pro-vitamins, such as beta-carotene,
alpha-carotene, gamma-carotene and the like; neovitamins, such as
neovitamin A; hydrocarbons, such as squalene, gaducene, pristane, zamene
and citorhenene, and the like; other long-chain fatty acids, such as
restim, alkoxydiglycerides, essential fatty acids, omega-9 fatty acids and
the like; sterols; phosphatides and the like.
The oil composition, fraction or combination of the present invention is
stably deodorized by admixture with an amount of a deodorizing agent
sufficient to substantially reduce the characteristic odor of the oil.
Exemplary of such deodorizing agents are aloe compositions and the like.
Aloe compositions useful in the practice of the present invention may be
obtained from a variety of species of aloe plants, such as Aloe
scototrina, Aloe Perryi Baker, Aloe ferox, Aloe africana, Aloe spicata,
Aloe perfoliata, Aloe Vera, Aloe vulgaris, Aloe barbadensis and the like.
Aloe vera, the preferred aloe useful in the present invention, may also be
obtained from a variety of commercial sources. While aloe vera available
from each manufacturer varies somewhat regarding a number of
characteristics, such commercially available substances are useful in the
compositions of the present invention. For example, aloe vera is
commercially available in hydrophilic and lipophilic forms, and both of
these forms may be used in accordance with the present invention.
Moreover, commercially available aloe vera is often dispersed within a
carrier, such as IPM (i.e., isopropyl myristate), IPP (i.e., isopropyl
palmirate), and the like. Other commercial "carrier" forms of aloe
compositions feature aloe stabilized in a water-soluble gel, such as
Veragel.RTM. and in a highly concentrated powder form (i.e., Veragel.RTM.
200). Both Veragel.RTM. products are available from Dr. Madis
Laboratories, Incorporated. Each of these "carrier/aloe" compositions may
also serve as the aloe constituent of stable, deodorized oil compositions
of the present invention.
The aloe and oil starting materials are preferably combined in a ratio of
from about 1:1 to about 50:1 by weight, aloe vera to the oil composition,
fraction or combination thereof. Higher ratios would also function in
accordance with the present invention. More preferably, the combination is
in a ratio of from about 1:1 to about 15:1 by weight aloe vera to oil
composition, fraction or combination thereof, with a ratio from about 1:1
to about 5:1 still more preferred. Guidelines for the use of commercially
available aloe vera formulations follow. Aloe in combination with
substances, such as IPM and IPP (i.e., aloe in a lipophilic carrier),
gives best results when admixed with oil in an aloe:oil ratio of from
about 1:1 to about 4:1, although higher ratios may be used in the practice
of the present invention. Gels containing aloe dispersed therein (i.e.,
aloe in a hydrophilic carrier) are preferably admixed with oil in an
aloe:oil ratio of from about 2:1 to about 6:1, although higher ratios may
be used in the practice of the present invention. The aloe/oil mixture may
be accomplished in any conventional manner sufficient to provide adequate
admixture thereof.
Increased stability is provided to the deodorized oil of the present
invention in comparison to that of prior art products. This enhanced
stability is due, at least in part, to the nature of the deodorization
process of the present invention. Merely admixing an aloe composition in
one of its many forms does not result in undesired side reactions which
modify the chemical structure and/or function of the components of the oil
composition. Moreover, the conditions under which the mixing takes place
are mild and do not disrupt the chemical structure and/or function of the
components of the oil composition. As a result, natural antioxidants
contained within the oil composition are not degraded and, consequently,
the deodorized oil is less likely to undergo autoxidation upon exposure to
air.
The stable, deodorized oil of the present invention also exhibits enhanced
penetration capability in comparison to prior deodorized oil products. One
reason for the enhanced penetration characteristics is that the
deodorization process of the present invention permits the components of
the oil composition to remain substantially intact (i.e., unchanged). In
other words, the components of the oil composition are maintained in their
natural form throughout the deodorization process. Orally delivered
omega-3 fatty acids, for example, are known to be incorporated into cell
membranes of platelets and endothelial cells. See, for example, Mueller
and Talbert, Clin. Pharm., 7(11): 795-807 (November 1988). Thus, the
natural, substantially intact form of these fatty acids is recognized by
the cells to such an extent that these fatty acids are incorporated into
the cell structure. Other components of the compositions, such as
phosphatides, vitamins and the like are also recognized by cells. This
cellular recognition aids in the penetration of the deodorized oil into
interior cells when applied to an exterior cellular surface, such as the
skin.
In addition, mixture of aloe vera with the oil composition does not occur
under conditions that are conducive to isomerization of omega-3 fatty
acids or other oil components. Such isomers may be created via oxidation,
hydrogenation, partial hydrogenation, high temperature processing and like
reactions involving the oil composition. For example, U.S. Pat. No.
4,843,095 indicates that saponification reactions converting triglyceride
oil components to free fatty acids, if conducted under certain conditions,
result in isomerization by cis-trans conversion. Such isomers are not
recognized by cells to the same extent as the natural isomeric form(s) of
oil composition components. Also, prior oil compositions were stabilized
by hydrogenation. Isomers created in this stabilization process are not
recognized by the body to the extent that the substantially intact,
polyunsaturated, natural form of the fatty acid is recognized.
Consequently, oil compositions containing cis-trans, hydrogenated or other
isomers of natural oil composition components would not exhibit the
enhanced penetration characteristics of deodorized oils of the present
invention. Furthermore, oxidation of polyunsaturated fatty acids can lead
to the formation of epoxides. Such epoxides are harmful to biomolecules,
particularly proteins and nucleic acids. Thus, oxidation of fatty acid oil
components reduces the usefulness of such an oil as a component in topical
compositions.
Finally, the deodorization process of the present invention permits the
non-fatty acid components of oil compositions of the present invention to
remain intact and functional. For example, substantially intact vitamins
present in the compositions of the present invention, such as vitamin A,
E, D and the like, function as previously described. Substantially intact
pro-vitamins present in the compositions of the present invention, such as
alpha-, beta- and gamma-carotene and the like, function as previously
described. Neovitamins, such as provitamin A, phosphatides and sterols
function as described above, when substantially intact and present in
compositions of the present invention. Substantially intact hydrocarbons,
such as squalene, gaducene, pristane, zamene and citorhenene and the like,
function as described above, when dispersed in compositions of the present
invention. Substantially intact non-omega-3 fatty acids, such as omega-9
fatty acids, essential fatty acids, restim, glycerol ethers (i.e.,
alkoxydiglycerides) and the like, function as previously described, when
dispersed in compositions of the present invention. Loss of these
functions due to conventional chemical deodorization processing decreases
the usefulness of the resultant deodorized product.
Another aspect of the present invention features compositions containing
stable, deodorized oils. For example, the stable, deodorized oils of the
present invention may be administered in oral dosage forms, such as in
liquid or in capsule form. Adjuvants known in the art for use in oral
dosage forms may be admixed with the stable, deodorized oils of the
present invention to produce oral dosage forms by a practitioner in the
art.
Preferred compositions of the present invention are stable topical
compositions having enhanced penetration properties. The topical
compositions of the present invention include an oil composition, wherein
the oil is characterized by an unpleasant odor, or a fraction of an oil so
characterized or a combination of oils or fractions thereof so
characterized; an amount of deodorizing agent effective to substantially
reduce the odor of said oil, fraction or combination thereof; and at least
one adjuvant suitable for topical use that does not adversely impact the
structure and/or function of the oil, fraction or combination thereof.
Preferably, oil compositions of the present invention include an omega-3
fatty acid component.
The enhanced penetration capability of topical compositions of the present
invention appears to result, in part, form the maintenance of certain oil
composition components in their natural states that are recognized by
cells in vivo. This increase in cellular recognition enhances the
penetration of a topical composition containing the recognized substances.
Increases in oil content of the topical composition also contribute to the
enhanced penetration capability of the topical compositions of the present
invention.
As adjuvants useful in the present invention, standard adjuvants such as
those utilized in cosmetic or pharmaceutical topical agents are
contemplated, so long as the adjuvants are suitable for topical use and do
not disrupt the structure and/or function of the oil composition.
Exemplary adjuvants are thickeners, emulsifiers, humectants,
anti-bacterials, emollients, ultraviolet absorbers, antibiotics,
antioxidants, antihistamines, fungicides, disinfectants, dyes,
pearlescents, keratolytic agents, absorbants, anti-caking agents and the
like. For a more exhaustive list of typical adjuvants, see McCutcheon's
1982 Functional Materials.
Exemplary thickeners are water soluble thickening agents, such as gum
arabic, karaya gum, gum tragacanth, guar gum, carob bean gum, tara gum,
pectines, algtnates, carraghenates, agar, furcellaria, starches and the
like; cellulose derivatives, such as methylcellulose, hydroxymethyl
cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,
hydroxypropylmethyl cellulose and the like; synthetic polymers, such as
sodium polyacrylate, polyvinyl alcohol, carboxylic polymer derivatives of
acrylic acid; and the like.
Emulsifiers used in topical compositions according to the present invention
may be anionic, cationic or non-ionic. Exemplary anionic emulsifiers are
alkali or alkaline earth soaps, such as sodium stearate, calcium oleate
and the like; soaps of organic bases; sulfate or sulfone salts, such as
sodium lauryl sulfate; and the like. Exemplary cationic emulsifiers are
quaternary ammonium salts, such as benzalkonium chloride and cetyl
pyridinium chloride, and the like. Exemplary non-ionic emulsifiers are
aliphatic fatty alcohols, such as cetyl alcohol, stearyl alcohol and the
like; fatty alcohols or alpha-diols, either oxyethylenated or
polyglycerolated; cyclic fatty alcohols; glycol esters of fatty acids,
such as ethylene glycol stearate, mono- or di-stearates of glycerol and
the like; polyethyleneglycol esters of fatty acids, such as polyethylene
glycol stearate and the like; esters of fatty acids of sorbitan; sucrose
esters of fatty acids; and the like.
Additional ingredients, such as perfumes or other odor masking compounds
may also be added to the compositions of the present invention.
Fragrances, perfuming agents and other odor-masking compounds are known
and readily available.
Since the oil compositions of the present invention exhibit enhanced
penetrating abilities, the penetration of adjuvants and other composition
components will also be enhanced. In cosmetic applications, cosmetic
ingredients that exhibit beneficial properties will penetrate the outer
dermal layers with greater efficiency and speed. This enhanced penetration
will lead to improved absorption of desireable ingredients, such as
hyaluronic acid, collagen, lanolin, cocoa butter, calendula oil, avocado
oil, apricot kernel oil, vitamin E, herb extracts, yucca, jojoba oil and
the like. In medicinal applications, enhanced absorption of efficacious
molecules will be achieved. The medicinal benefit of enhanced penetration
of a topical agent can be garnered in treatment of both animals and
humans.
A typical adjuvant formulation suitable for topical application in
accordance with the present invention is 3.0% (% by weight of total
composition) glycerol monostearate; 2.0% cetyl alcohol; 3.5% stearic acid;
0.10% propyl paraben; 1.0% jojoba oil; 2.0% isopropyl palmirate; 1.0%
triethanolamine; 4.0% propylene glycol; 0.15% methyl paraben and 80.0%
water.
Due to the level and duration of deodorization attainable in accordance
with the present invention, the oil composition component may constitute a
high percentage by weight of the total topical compositions. When the
present invention is practiced, the economic attractiveness of using water
as a component of a topical composition replaces oil composition odor as
the limiting factor with respect to the percentage of oil in that topical
composition. Preferably, topical compositions of the present invention
contain at least 2-3% by weight oil composition component with at least
10% Oil more preferred. Practically, an upward limit on the percentage of
oil composition within the topical compositions of the present invention
is approximately 50%. However, topical compositions containing higher
percentages can be prepared.
The topical compositions of the present invention may be prepared in
accordance with the following procedure: admixing the oil composition,
fraction or combination thereof with aloe; aging the mixture; and admixing
topical adjuvants with the aged mixture. Alternatively, topical
compositions in accordance with the present invention may be prepared by
the following method: admixing the oil composition, fraction or
combination thereof, aloe and topical adjuvants; and aging the mixture.
Mixing steps in both methods may be accomplished under appropriate mild
conditions and in accordance with known techniques.
Aging the oil:aloe mixture or the topical composition as a whole may allow
interactions between components to take place slowly in the absence of the
application of high temperatures or other harsh reaction conditions. The
choice of the best preparation methodology for use with a specific
formulation is dependent upon the nature of the aloe used. If the aloe is
lipophilic, the oil:aloe mixture is preferably aged prior to mixture with
the topical adjuvant(s). Otherwise, the complete topical composition is
aged. In either event, the duration of the aging process is the same,
i.e., from about 3 to about 14 days, with from about 6 to about 10 days
preferred. The deodorization proceeds gradually during the aging process
which is preferably carried out under anaerobic conditions.
Optionally included within the topical compositions of the present
invention are pharmaceutically active agents capable of dispersion within
the topical composition and which impart pharmaceutical benefit to the
area of the body to which the agent is applied or to an area physically or
systemically interrelated therewith. That is, if the topical composition
is applied to a specific skin area, the pharmaceutically active ingredient
must either act on the skin itself, penetrate the skin to act on deep soft
tissues, joints, bursers, ligaments, tendons, muscles, and the like, or
penetrate into the bloodstream to be carried to the afflicted area.
Exemplary pharmaceutically active agents are those that are capable of
imparting anti-inflammatory, analgesic, vasodilatory, anti-pruritic,
anesthetic, protectant, counterirritant, astringent, antiseptic,
keratolytic, anticholinergic, antihistamine, wound healing and like
pharmaceutical benefits to an afflicted area. Methyl salicylate,
benzocaine, dibucaine, phenylephrine hydrochloride, zinc oxment kaolin,
calamine, camphor, menthol, salicylic acid, coal tar, allantoin, live
yeast cell derivatives, boric acid, phenol, resorcinol, precipitated
sulfur, afropine, juniper tar, hydrocortisone and the like are exemplary
pharmaceutically active agents useful in accordance with the present
invention.
Exemplary ailments which may be treated using a topical composition of the
present invention in admixture with a pharmaceutically active agent are
bursiris, tendonitis, epicondylitis, myofacial pain syndrome, myositis,
degenerative and inflammatory arthritis, vasospastic disorders, neck pain,
lower back pain, sciatica, post exercise pain, post operative swelling,
burns, diaper rash, itching, acne, sunburn, windburn, fever blister, cold
sore, insect bite, insect sting, poison ivy, poison oak, poison sumac,
anorectal disorders, dermatitis, such as seborrheic dermatitis, psoriasis,
fungus, other skin conditions, such as some types of skin discoloration,
ophthalmic disorders, and the like. A topical composition of the present
invention may also be used as a carrier for sunscreening agent, such as
para-aminobenzoic acid, octyl dimethyl para-aminobenzoic acid, cinoxate,
homosalate, octyl methoxycinnamate and the like and, additionally, as a
carrier for agents screening against precancerous and/or
cancerous-inducing lesions and the like.
Local anesthetics, for example, may be included is pharmaceutical
compositions formulated for the treatment of burns, insect bites or
stings, sunburn, and the like. Exemplary local anesthetics are benzocaine,
dibucaine, benzyl alcohol, dibucaine hydrochloride, lidocaine, pramoxine
hydrochloride, tetracaine, and tetracaine hydrochloride.
Analgesic, anesthetic and antipuritic compounds may also be included within
pharmaceutical compositions. Exemplary of such compounds are juniper tar,
camphor, menthol, and methyl salicylate. At higher concentrations, these
compounds act as counterirritants and increase circulation.
Topical compositions for the treatment of conditions, such as seborrheic
dermatitis, psoriasis, and the like, may also be formulated in accordance
with the present invention. Such compositions would include pyrithione
zinc, salicylic acid, selenium sulfide, sulfadiazine, sulfur, or a
combination thereof.
An exemplary antibiotic cream of the present invention includes a neomycin
sulfate active ingredient. Exemplary anti-ache compositions of the present
invention contain sulfur or zinc oxide active agents. An exemplary
anti-inflammatory, anti-inch composition of the present invention includes
a hydrocortisone acetate active ingredient. Also, an exemplary liniment
composition of the present invention includes at least one active agent
selected from menthol, camphor, and eucalyptol.
The amount of a specific active pharmaceutical ingredient or ingredients
included within a pharmaceutical topical composition of the present
invention is dependent upon a variety of factors, such as the miscibility
of the pharmaceutical, the stabilized oil, and the adjuvants, the typical
effective dose of the pharmaceutical, and the like. Generally, the amount
of a pharmaceutical ingredient included within a topical composition will
range from about 0.1% to 5% by weight of that composition, with from about
2% to about 20% being preferred. For methyl salicylate, for example, the
topical composition will include from about 5% to 20% by weight of the
pharmaceutical, with from about 10% to about 15% being preferred.
The present invention also contemplates general topical skin protectant
compositions. A skin protectant is defined by the Food and Drug
Administration as "[a]drug which protects injured or exposed skin or
mucous membrane surface from harmful or annoying stimuli." Exemplary skin
protectants and approximate active percentages follow:
allantoin (from about 0.5% to about 2.0% by weight).
aluminum hydroxide gel (from about 0.15% to about 5.0% by weight).
calamine (from about 1.0% to about 254 by weight).
cocoa butter (from about 50% to 100% by weight).
dimethicone (from about 1.0% to about 30% by weight).
kaolin (from about 4.0% to about 20% by weight).
zinc acetate (from about 0.1% to about 2.0% by weight).
zinc carbonate (from about 0.2% to about 2.0% by weight).
zinc oxide (from about 1.0% to about 25% by weight).
For a protectant for use with minor cuts, scrapes, and burns including
sunburn, allantoin and/or cocoa butter are exemplary preferred active
ingredients. For prevention and treatment of chafed, chopped, cracked or
windburned skin and lips, exemplary preferred active ingredients are
allantoin and/or cocoa butter and/or dimethicone. To dry poison ivy,
poison oak, and poison sumac, compositions containing one or more
exemplary preferred active ingredients, such as aluminum hydroxide gel,
calamine, kaolin, zinc acetate, zinc carbonate, and zinc oxide.
The amount of the pharmaceutical topical composition applied and the number
of applications thereof is dependent on a number of factors. Primarily,
the treatment will be dictated by the patient's condition and therapeutic
response to the treatment. A clinician would be able to ascertain an
appropriate treatment protocol. Typically, the topical composition will be
administered twice daily for 7 to 10 days; however, more or less frequent
administration and/or shorter or longer treatment duration may be employed
in accordance with-sound medical practices.
Moisturizer Formulation. To form a moisturizing composition in accordance
with the present invention, three compositions, designated A, B and C are
formed as follows:
______________________________________
% By Weight
Composition
Ingredient Total Composition
______________________________________
A Shark Liver Oil
3.0
Jojoba oil 1.0
Isopropyl Palmitate
2.0
Cetyl Alcohol 2.0
Stearic Acid XXX*
3.5
Glycerol Monostearate
3.0
Propyl Paraben 0.10
B Triethanolamine
1.0
Aloe Veragel .RTM. 200**
0.25
Propylene Glycol
4.0
Methyl Paraben 0.15
Water 80.0
C Fragrance q.s.
______________________________________
*Triple pressed stearic acid.
**Aloe concentrated 200 times available from Dr. Madis Laboratories,
Incorporated.
q.s. = quantity sufficient.
Composition A is heated at 80.degree. C. and admixed until uniform.
Composition B is heated at 80.degree. C. and admixed until a solution is
formed. Composition B is slowly added to composition A under agitated
conditions. Agitation is continued at a slow rate and the combined
composition is allowed to cool to 45.degree. C. Composition C is added and
agitation is continued while the composition is allowed to cool to
30.degree. C. The mixture is aged at 20.degree. C. for 10 days, resulting
in a composition with an acceptable odor for topical applications.
Analgesic Cream. To form an analgesic composition in accordance with the
present invention, four compositions, designated A, B, C and D are formed
as follows:
______________________________________
% By Weight
Composition
Ingredient Total Composition
______________________________________
A Cod Liver 5.0
Veragel .RTM. Lipoid 1:1*
5.0
B Glycerol Monostearate
3.0
Cetyl Alcohol 2.35
Stearic Acid XXX
4.0
Propyl Paraben 0.10
C Menthol 0.10
Camphor 0.20
Oil of Eucalyptus
0.10
D Triethanolamine
1.0
Propylene Glycol
3.0
Methyl Paraben 0.15
Water 76.0
______________________________________
*From Dr. Madis Laboratories, Incorporated.
The ingredients in composition A are admixed and permitted to age at
20.degree. C. for 4 days to produce a composition with an odor acceptable
for topical applications. Composition D is heated to 60.degree. C.
Composition B is added to D slowly, and the admixed compositions are
agitated until the resultant composition is uniform. Composition A is
slowly added to the combined D/B composition, and agitation is continued
while the D/B/A mixture is cooled to 45.degree. C. Composition C is added,
and the composition is agitated while being cooled to 30.degree. C.
Burn Cream. To form a burn treatment composition in accordance with the
present invention, three compositions, designated A, B and C are formed as
follows:
______________________________________
% By Weight
Composition
Ingredient Total Composition
______________________________________
A Fish Oil Fraction
10.0
Aloe Vera Gel* 45.0
B Isopropyl Myristate
2.0
Cetyl Alcohol 2.5
Glycerol Monostearate
3.0
Benzocaine 2.05
Propyl Paraben 0.10
C Triethanolamine
1.0
Propylene Glycol
4.0
Allantoin 0.2
Water 30.0
Methyl Paraben 0.15
______________________________________
*From Golden Horizons International, Limited.
The ingredients of composition A are mixed until uniform, and aged for 5
days, resulting in a composition with an odor acceptable for topical
applications. Composition C is heated to 80.degree. C. Composition B is
added to composition C slowly and the B/C mixture is cooled to 45.degree.
C. under agitation. Composition A is added to the cooled B/C mixture and
agitation is continued until the topical composition has cooled to
30.degree. C.
Cosmetic Application Protocol. A moisturizing cream prepared in accordance
with the procedure described above may be applied to the skin of a user
having dry skin twice daily to enhance the vitality of the skin to which
the cream is applied.
Therapeutic Protocol A. An analgesic composition prepared in accordance
with the procedure described above may be administered by topical
application to the injured area of a patient suffering from a
sports-related tendon injury twice a day for ten days or less. Pain relief
is expected to be observed.
Therapeutic Protocol B. An analgesic composition prepared in accordance
with the procedure described above may be administered by topical
application to the injured area of a patient suffering from a rheumatoid
arthritis twice a day for ten days or less. Pain relief is expected to be
observed.
Therapeutic Protocol C. A burn cream prepared in accordance with the
procedure described above may be administered by topical application to
the burn of a patient suffering from a third degree burn twice a day for
ten days or less. Pain relief is expected to be observed.
Patient Trial Results
Analgesic pharmaceutical formulations containing shark oil and aloe vera
within the percentages set forth above and approximately 10% by weight
methyl salicylate were prepared substantially in accordance with the
procedure described above. The pharmaceutical formulations were
administered twice daily to patients suffering from a variety of medical
problems. Table I indicates the patient's global assessment of their
response to the topical composition (4=excellent; 3=Good; 2=Fair; 1=None).
TABLE I
______________________________________
Patient ID Diagnosis Response
______________________________________
BJ RA 3
DW F, TE, B 3
JM RA, F 4
EB F, TE, B 4
BG F, B 4
NW RA, B 3
EM F, TE, B 3
AM OA, F, B 3
SS F, TE 3
CB F, S, B 3
NR F, TE 3
AD OA 4
TO B 3
GP OA, F 3
PF F 3
MP OA, F 3
DC F, TE, B 3
AT OA, F 3
GM OA 4
JM F, B, TE 4
VS B 3
GA RA, B 3
DR F, TE 4
FH RA 3
LL RA 4
JC RA, B 3
GF RA, F 3
EL RA 3
KG F, TE 4
JW F 2
FK OA, F 4
BR RA 2
NB F, TE 2
HK OA, B 3
BP TE 4
SK PA 4
EM TE, B 3
LL F 3
PF F 4
EA F, OA 4
GD OA 3
LG RA 4
JA OA 2
CE RA, F 3
JR F 4
CF F, B, TE 3
MS OA 3
DD TE, B 3
SB B, F 4
KG F, B 4
BG F 3
IS F, RA 4
LU F, OA 3
EF B 3
MZ F 2
GB F 3
KR B, RA 2
EF F, RA 3
AL B, TE 0
LJ F, B 4
VQ B 0
JR F 2
CG B 4
BH B 3
AB F 3
JB OA 4
PA OA 4
SS OA 3
VH F 4
BC OA, F 3
JB OA 4
PA OA 4
CR OA, F 4
GR OA, F 4
MS F 4
RE F 3
AO F 3
GP RA 4
AK RA 4
LK OA 4
GL F, B 3
CF F 0
BF OA 4
MP F 2
KK OA 2
FC OA 3
DH B 3
JA OA, F 3
LH B 4
GW F, B, OA 4
GH F, OA 1
RE F 3
DM F, B 3
HH T 3
______________________________________
(OA = Osteoarthritis; RA = Rheumatoid Arthritis; F = Fibrositis,
Fibromyalgia, Musculoskeletal Pain, and Soft Tissue Rheumatism; B =
Bursitis; TE = Tennis Elbow; S = Sjogren's Syndrome; PA = Psoriatic
Arthritis)
The results indicate that 86% of the patients treated with the topical
medicament exhibited good to excellent therapeutic responses.
While in the foregoing specification this invention has been described in
relation to certain preferred embodiments thereof, and many details have
been set forth for purposes of illustration, it will be apparent to those
skilled in the art that the invention is susceptible to additional
embodiments and that certain of the details described herein may be varied
considerably without departing from the basic principles of the invention.
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